Bisabosquals, Novel Squalene Synthase Inhibitors: I. Taxonomy, Fermentation, Isolation and Biological Activities

• Published in: Journal of antibiotics 2001/11/25, Vol.54(11), pp.890-895
• Main Authors: MINAGAWA, KAZUYUKI, KOUZUKI, SHUICHI, NOMURA, KAZUHIDE, YAMAGUCHI, TAKAHIRO, KAWAMURA, YOSHIMI, MATSUSHIMA, KEISUKE, TANI, HIROYOSHI, ISHII, KIKUO, TANIMOTO, TATSUO, KAMIGAUCHI, TOSHIYUKI
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Applied microbiology; Biological and medical sciences; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Farnesyl-Diphosphate Farnesyltransferase - antagonists & inhibitors; Fermentation; Fundamental and applied biological sciences. Psychology; Hepatocytes; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Microbiology; Pyrans - isolation & purification; Pyrans - pharmacology; Rats; Stachybotrys - chemistry; Stachybotrys - classification; Stachybotrys - metabolism
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.54.890

In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5μg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.